Immuno-genetics has shown that when a cell differentiates, the structure of its surface undergoes specific changes that must reflect a program of gene regulation governing that particular pathway of differentiation. Knowledge of how such programs are initiated may be of great value in elucidating mechanisms involved in the genetic determination of cellular differentiation and morphogenesis. A unique opportunity to study this problem is provided by our observation that a product of the thymus can, in vitro, rapidly induce precursor cells from mouse spleen or bone marrow to differentiate into T-lymphocytes, bearing T marker antigens (TL, Thy-1 and the Ly series). We see this as a possible model of a multiple gene regulation in induction/differentiation systems generally; its assets being simplicity and the already-existing detailed knowledge of the genetic loci (at least five) concerned. This is vitro T cell induction system will be used to study in the mouse: (1) The chemistry and specificity of the thymic inducer (TI) and its receptor. (2) Sources of the inducer with regard to species, organ, age and physiological state. (3) Origins and location of precursor cells. (4) The relationship of inducer to the entire sequence of T-cell differentiation. (5) The relation of induction to expression of leukemia virus and leukemia virus antigens.